rs2273346

Positions:

chr1-11030840-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006610.4(MASP2):c.1130T>C(p.Val377Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,613,664 control chromosomes in the GnomAD database, including 2,381 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 551 hom., cov: 32)

Exomes 𝑓: 0.031 ( 1830 hom. )

Consequence

MASP2
NM_006610.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.97

Variant links:

Genes affected

MASP2 (HGNC:6902): (MBL associated serine protease 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is proteolytically processed to generate A and B chains that heterodimerize to form the mature protease. This protease cleaves complement components C2 and C4 in order to generate C3 convertase in the lectin pathway of the complement system. The encoded protease also plays a role in the coagulation cascade through cleavage of prothrombin to form thrombin. Myocardial infarction and acute stroke patients exhibit reduced serum concentrations of the encoded protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

MASP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020970702).

BP6

Variant 1-11030840-A-G is Benign according to our data. Variant chr1-11030840-A-G is described in ClinVar as [Benign]. Clinvar id is 291785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASP2	NM_006610.4 linkuse as main transcript	c.1130T>C	p.Val377Ala	missense_variant	9/11	ENST00000400897.8	NP_006601.2
MASP2	XR_001736931.1 linkuse as main transcript	n.1083T>C		non_coding_transcript_exon_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000400897.8 linkuse as main transcript	c.1130T>C	p.Val377Ala	missense_variant	9/11	1	NM_006610.4	ENSP00000383690	P1	O00187-1

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

9126

AN:

152018

Hom.:

550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0365

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.00999

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.0632

GnomAD3 exomes

AF:

0.0502

AC:

12612

AN:

251006

Hom.:

761

AF XY:

0.0504

AC XY:

6844

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.0229

Gnomad ASJ exome

AF:

0.0403

Gnomad EAS exome

AF:

0.210

Gnomad SAS exome

AF:

0.0930

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.0188

Gnomad OTH exome

AF:

0.0402

GnomAD4 exome

AF:

0.0308

AC:

45045

AN:

1461528

Hom.:

1830

Cov.:

AF XY:

0.0325

AC XY:

23642

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.0242

Gnomad4 ASJ exome

AF:

0.0431

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.0921

Gnomad4 FIN exome

AF:

0.00975

Gnomad4 NFE exome

AF:

0.0176

Gnomad4 OTH exome

AF:

0.0455

GnomAD4 genome

AF:

0.0601

AC:

9148

AN:

152136

Hom.:

551

Cov.:

AF XY:

0.0613

AC XY:

4562

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.0364

Gnomad4 ASJ

AF:

0.0349

Gnomad4 EAS

AF:

0.205

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.00999

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.0634

Alfa

AF:

0.0306

Hom.:

368

Bravo

AF:

0.0642

TwinsUK

AF:

0.0210

AC:

ALSPAC

AF:

0.0200

AC:

ESP6500AA

AF:

0.128

AC:

564

ESP6500EA

AF:

0.0181

AC:

156

ExAC

AF:

0.0528

AC:

6413

Asia WGS

AF:

0.133

AC:

460

AN:

3478

EpiCase

AF:

0.0229

EpiControl

AF:

0.0238

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency due to MASP-2 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.25

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.3

REVEL

Benign

0.15

Sift

Benign

0.051

Sift4G

Benign

0.081

Polyphen

0.0020

Vest4

0.044

MPC

0.048

ClinPred

0.012

GERP RS

2.8

Varity_R

0.32

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over